Studies on the effects of circulatory shock, tissue ischemia, and sublethal tissue hypoxia on cell metabolism and cation balance are proposed. In addition to in vivo shock, ischemia and hypoxia, in vitro model systems of perfused organs and isolated intact cells will be utilized. Cellular alterations will be characterized by in situ monitoring of mitochondrial redox level and extracellular pO2, pH and K ion activities. Respiratory, ATP synthetic, and ion transport capacities and enzyme concentrations and activities will be determined in isolated mitochondria. Therapeutic interventions capable of modifying these cellular responses will be sought. Correlation of whole body, cellular and subcellular parameters will be utilized to clarify the cause and effect relationships of the cellular alterations involved in ischemic injury. The mechanism of mitochondrial adaptation to altered tissue oxygenation will be investigated.